EXPRESSION AND CATALYTIC ACTIVITIES OF PROTEIN-TYROSINE KINASES (PTKS) FYN AND LCK IN PERIPHERAL-BLOOD T-CELLS FROM ELDERLY HUMANS STIMULATED THROUGH THE T-CELL RECEPTOR (TCR) CD3 COMPLEX/

Optimal signal transduction through the T cell receptor (TCR)/CD3 comp lex requires the coordinated activities of protein tyrosine kinases (P TKs) Fyn and Lck in addition to protein tyrosine phosphatases (PTPases ) such as CD45. Although T cells stimulated with anti-CD3 monoclonal a ntibodies (mAb) exhibit age-related reductions in tyrosine phosphoryla tions of cellular proteins, it is unknown if the reductions represent abnormalities in PTKs or PTPases. In the current studies, immune compl ex kinase assays showed that the stimulation of peripheral blood T (PE T) cells from young humans with cross-linked anti-CD3 epsilon mAb OKT3 induced increased Fyn catalytic activity while anti-CD3 stimulation f ailed to induce significant increases in Lck activation. By contrast, Fyn activation in anti-CD3 stimulated PET cells from a substantial pro portion of elderly humans was reduced compared to anti-CD3 stimulated PET cells from young humans. Also, we failed to fmd any increase in an ti-CD3 stimulation of Lck activity in PET cells from elderly subjects that could compensate for the decline in Fyn activity. However, no age -related alterations were detected in PET cell expression of Fyn or Lc k that might contribute to the changes in enzymatic activity. The resu lts of other experiments demonstrated that the functional activities o f PTPases in PET cells from elderly subjects were equivalent to PET ce lls from young subjects. These observations suggest that aberrant regu lation of TCR/CD3 coupled PTKs may contribute to the age-related defec ts in signaling cascades and immune responsiveness of human T cells. ( C) 1997 Elsevier Science Ireland Ltd.